title: Scara1 deficiency impairs clearance of soluble amyloid-β by mononuclear phagocytes and accelerates Alzheimer's-like disease progression.
abstract: In Alzheimer's disease, soluble amyloid-β causes synaptic dysfunction and neuronal loss. Receptors involved in clearance of soluble amyloid-β are not known. Here we use short hairpin RNA screening and identify the scavenger receptor Scara1 as a receptor for soluble amyloid-β expressed on myeloid cells. To determine the role of Scara1 in clearance of soluble amyloid-β in vivo, we cross Scara1 null mice with PS1-APP mice, a mouse model of Alzheimer's disease, and generate PS1-APP-Scara1-deficient mice. Scara1 deficiency markedly accelerates Aβ accumulation, leading to increased mortality. In contrast, pharmacological upregulation of Scara1 expression on mononuclear phagocytes increases Aβ clearance. This approach is a potential treatment strategy for Alzheimer's disease.
authors.affiliation: Department of Neurobiology, Sagol School of Neuroscience, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 699788, Israel.
authors.forename: Dan
authors.initials: D
authors.lastname: Frenkel
authors.forename: Kim
authors.initials: K
authors.lastname: Wilkinson
authors.forename: Lingzhi
authors.initials: L
authors.lastname: Zhao
authors.forename: Suzanne E
authors.initials: SE
authors.lastname: Hickman
authors.forename: Terry K
authors.initials: TK
authors.lastname: Means
authors.forename: Lindsay
authors.initials: L
authors.lastname: Puckett
authors.forename: Dorit
authors.initials: D
authors.lastname: Farfara
authors.forename: Nathan D
authors.initials: ND
authors.lastname: Kingery
authors.forename: Howard L
authors.initials: HL
authors.lastname: Weiner
authors.forename: Joseph
authors.initials: J
authors.lastname: El Khoury
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D018955:CD36 Antigens / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000494:pharmacology; D018450:Disease Progression; D004338:Drug Combinations; D057809:HEK293 Cells; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D010586:Phagocytes / Q000187:drug effects / Q000378:metabolism*; D053764:Presenilin-1 / Q000378:metabolism; D059748:Proteolysis / Q000187:drug effects; D034741:RNA, Small Interfering / Q000378:metabolism; D051117:Scavenger Receptors, Class A / Q000172:deficiency* / Q000378:metabolism; D012995:Solubility; D016019:Survival Analysis; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016229:Amyloid beta-Peptides; D018955:CD36 Antigens; D004338:Drug Combinations; D008070:Lipopolysaccharides; C495140:Msr1 protein, mouse; D053764:Presenilin-1; C493785:Protollin; D034741:RNA, Small Interfering; D051117:Scavenger Receptors, Class A; D003546:Cysteine Endopeptidases